7. PROJECT SUMMARY/ABSTRACT In this Exploratory/Developmental project we test the idea that changes in the gut microbiota, by regulating host immune cells, can influence periprosthetic joint infection. Although incidence of periprosthetic joint infection is less than 1%, infection is the number one cause of revision total knee arthroplasty and the third leading cause of revision total hip arthroplasty. Existing treatments for periprosthetic joint infection are expensive in terms of cost and patient morbidity and have low success rates, suggesting the need for improved methods of preventing infection. One factor recently associated with infection is the patient microbiome. Alterations in the gut microbiome have been observed in almost all clinical conditions identified as risk factors for periprosthetic joint infection (diabetes, malnutrition, obesity, etc.). The gut microbiome is a key mediator of the host immune system. Patients with impaired gut microbiota are at greater risk for infection following stem cell transplantation and animal models suggest that a history of a healthy microbiome improves resistance to systemic infection. Our hypothesis is that altered gut microbiota reduce immune cell populations and thereby facilitate the development of periprosthetic joint infection. The project has one aim: Determine the severity of periprosthetic infection in mice with altered gut microbiota. In this project we combine a novel murine model of periprosthetic joint infection with manipulation of the gut microbiota. We consider four conditions of the gut microbiome: 1) normal microbiome; 2) altered microbiome due to genetic background; 3) altered microbiome due to history of antibiotic treatment; and 4) a history of no microbiome (germ-free). We then determine the severity of implant infection, the contents of the gut microbiota and the associated changes in immune cell populations. If our hypothesis is correct it will suggest that the gut microbiome is a modifiable risk factor for periprosthetic joint infection, and that treatments reconstitution of a healthy gut microbiota prior to total joint arthroplasty could further risk the risk of infection.